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Hepatic Expression of SV40 Small-t Antigen Blocks thein VivoCD95-Mediated Apoptosis

Authors
Journal
Biochemical and Biophysical Research Communications
0006-291X
Publisher
Elsevier
Publication Date
Volume
284
Issue
2
Identifiers
DOI: 10.1006/bbrc.2001.4988
Keywords
  • Apoptosis
  • Cd95/Fas
  • Sv40 Small-T Antigen
  • Akt
  • Liver
  • Transgenic

Abstract

Abstract We have previously demonstrated that CD95-mediated apoptosis of hepatocytes is blocked in a murine model of hepatocarcinogenesis due to the expression of SV40 early sequences encoding the large-T and small-t antigens. In this study, we set out to pinpoint the sequences involved in this apoptosis-resistant phenotype, and tested several mutants of the SV40 early region for their ability to confer protection against CD95-induced apoptosis in transgenic mice. We show that resistance to apoptosis is independent of the transforming character of the mutants and demonstrate that the expression of the small-t antigen alone in transgenic mice is sufficient to confer this resistance. Our data also reveal an increased level of activated Akt kinase in these transgenic mice, and this could account for this hitherto unknown function of the SV40 small-t antigen.

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